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Annals of Oncology 2006 17(Supplement 5):v13-v16; doi:10.1093/annonc/mdj942
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© 2006 European Society for Medical Oncology

symposium article

Pharmacogenomics and gemcitabine

R. Rosell1,*, M. Cobo2, D. Isla3, C. Camps4 and B. Massuti5

1 Catalan Institute of Oncology, Barcelona; 2 Hospital Carlos Haya, Malaga; 3 Hospital Lozano Blesa, Zaragoza; 4 Hospital General de Valencia, Valencia; 5 Hospital General de Alicante, Alicante, Spain

* Correspondence to: Dr R. Rosell, Chief, Medical Oncology Service, Scientific Director of Oncology Research, Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Ctra Canyet, s/n, 08916 Badalona, Spain. Tel: +34-93-497-89-25; Fax: +34-93-497-89-50; E-mail: rrosell{at}ico.scs.es

Approximately half of lung cancer patients present with metastases, and a large proportion will develop recurrent disease, with median survival to cisplatin-based chemotherapy of 11 months. No predictive factor of response to cisplatin-based chemotherapy is yet available in clinical practice. The nucleotide excision repair system plays a major role in repairing a variety of distorting lesions, notably platinum-induced DNA adducts. ERCC1 is a leading gene in repairing cisplatin DNA damage. We carried out three different studies examining individually the role of ERCC1, RRM1, and then both, mRNA expression in paraffin-embedded pretreatment bronchial biopsies from gemcitabine/cisplatin-treated advanced non-small-cell lung cancer (NSCLC) patients. Median survival was significantly prolonged in patients with low levels of ERCC1 or RRM1. BRCA1 is involved in homologous recombination repair, and we observed that low levels of BRCA1 mRNA significantly increased survival in gemcitabine/cisplatin-treated patients. Our observations lead us to recommend that tumors be regularly assessed for ERCC1 and BRCA1 mRNA expression in order to customize gemcitabine/cisplatin treatment.

Key words: BRCA1, cisplatin, ERCC1, gemcitabine, non-small-cell lung cancer, nucleotide excision repair


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